Hemorrhoidal composition



nitc States 3,019,1b3 Patented Jan. 30, 1962 3,019,163 IEMORRHOIDAL COMPOSITION Lucien Hamist, Rua Aperana 117, Rio de Janeiro- Leblon, Brazil No Drawing. Filed July 13, 1959, Ser. No. 826,400 5 Claims. (Cl. 167-63) The present invention relates to an ointment composition for the relief of hemorrhoids. More particularly the invention relates to an ointment comprising three meeting components, namely, an aluminum salt, an anesthetic, and a dispersing agent. These components coact with one another in such a way that they form a composition for the relief of pain and discomfort, itching and soreness, and burning sensations of the rectum and perianal areas due to hemorrhoids.

This application is a continuation-impart of my copending application Serial No. 662,332, filed May 29, 1957, for Ointment Composition, now abandoned.

In one embodiment of this invention the aluminum salt of alpha-hydroxypropionic acid, ethylamino benzoate, and dioctyl sodium sulphosuccinate are combined together in a bland base of polyethylene polyglycol to form a satis factory treatment composition for hemorrhoids.

The problem of nonsurgical treatment of hemorrhoids i is one which has plagued humanity and the medical profession for centuries. Naturally, surgical intervention relieves the particular affected area immediately. But there are a large number of patients that refuse surgery, have repeated recurrences, and cannot be controlled, for one reason or another, by the standard techniques of surgery. In addition, when preparing the patient for surgery, some relief must be afforded. It is this great group for which non-surgical treatments have been devised. The condition of hemorrhoids refers to a number of vascular tumors of the rectal mucous membrane. These varicosities (affectations of the vascular wall of the venous supply) which are internal if they occur above the sphincter ani and are external if they occur outside the sphincter. Most of the causes of this condition are not definitely known.

A number of factors are known condition but, like all affectations of the vascular system, the morbid condition is due to some internal cause which is undetermined among the human genetic factors.

Treatment of the condition has been largely empirical. The development of the surgical technics has been a fairly recent one. However, surgical technics are fraught with danger. The finst danger is that of infection, the second danger is that of uncontrolled bleeding, and the third danger is in inability to re-establish adequate circulation following surgery. In selected cases surgery has been simple and easy and an adequate answer to the problem. In other cases surgery has failed to limit further developmcnt of the disease, has limited circulation to the area, and has led to serious consequences. There are still other persons on which it is impossible to perform surgery, or who refuse surgery. It is this last large group to which much of the treatment by application of ointment has been directed.

For the treatment of external hemorrhoids the ointment is spread on the outer surface. For the treatment of internal hemorrhoids physicians have used measures which enable the ointment to be spread on the internal mucous surface. Among the mechanical instruments designed for this purpose there is a simple extended pipe with holes at the remote end. This is known as a pile pipe. In addition the ointment ingredients can be incorporated in a suppository base. This base in the form of a torpedo is inserted into the rectum above the sphincter in to contribute to the order to spread the composition on the surface of the rectal mucous membrane.

Treatment must be directed to three impotrant aspects of the disease. First, the surface of the affected vessels and the surface of the skin supplied (nutritionally) by these vessels must be toughened to prevent. bleeding. One of the most annoying and indeed dangerous, aspects of the hemorrhoidal condition is the tendency to constantly bleed and stain the clothing.

This composition, by reason of its contents of aluminum lactate in combination with the other ingredients, provides a means of so conditioning the vessel wall that bleeding is reduced to a minimum or is stopped entirely.

A second aspect of the treatment is that of decongestion. Because of the poor circulation, induced by blocking of the blood supply, fluids tend to collect and remain in the rectal tissues. This causes edema (swelling) of the organ and the perianal areas. Alleviation of this condi tion results in great relief of discomfort, especially since the edema tends to invade the surrounding supporting tissues. This composition, by reason of its effect onthe osmotic balance, causes reduction of edema. This decongestive effect is a special property of the aluminum lactate in combination with the dioctyl sodium sulphosuccinate.

The third, and from the patients point of view, the most important factor, is relief of itch and pain. This has been accomplished in the past by the use of caine derivatives such as the one used in this combination, but its use was always attended by a serious drawback. This serious limitation was the possibility of allergic reaction. In combination with the aluminum lactate, however, this drawback seems to be largely, if not entirely overcome. By means of a mechanism not thoroughly understood the caine derivative interacts with the aluminum lactate to give the basic action in the composition of the present invention. This action is further greatly enhanced and the beneficial action of the composition promoted while greatly reducing any possibility of undesired side actions by the further combination with the aluminum salt of alpha-hydroxypropionic acid (aluminum lactate) and the topical anesthetic such as ethylamino benzoate of a substance herein termed modifier which acts to pro-mote interaction between the other components. Dioctyl sodium sulphosuccinate is the most preferred substance of this type.

It is possible to substitute various anesthetics for the ethylamino benzoate, provided however the anesthetic sensitivity is controlled by the aluminum salt. The following caine derivatives have been found satisfactory as anesthetics for topical application incorporated in the compound of the present invention: (1) ethylamino benzoate (Benzocaine), (2) Z-diethyl amino ester of para aminobenzoic acid (Procaine), (3) 2-butoxy-n(2-diethyl aminoethyl) chroninamide hydrochloride (Di-bucaine), (4) 2-(isobutylamino)-ethyl para aminobenzoate hydrochloride (Monocaine), (5) Z-dimethyl amino ester of para butylamino benzoic acid. The preferred caine derivative is ethylamino benzoate (Benzocaine) and the preferred amount is 3%. Amounts of 5% or above have been found useful and amounts of 1% and. below have been used.

Dioctyl sodium sulphosuccinate is used as a modifier and plasticizer. Various modifiers have been tried and include the following: (1) cellulose ethers examples of which are sodium carboxymethylcellulose and methyl cellulose, (2) sodium salt dispersing agents examples of which are dioctyl sodium sulphosuccinate and sodium lauryl sulphate, (3) fatty acid esters of sugars examples of which are sorbitan mo-no-oleate and sorbitan monooleate polyester.

The preferred modifier is dioctyl sodium sulphosuccinate but others have been used with success. The preferred amount of modifier is one-half of one percent, amounts as high as 1% and above may be used and amounts of one-fourth of one percent and less have been used.

The aluminum salt utilized in this composition is the aluminum salt of alpha-hydroxypropionic acid. The preferred amount of aluminum salt is 2%. Amounts as high as 8% have been used and amounts above 8% can be used. Amounts of 1% and less have been successfully used.

The ointments are usually made in a water base. Oil bases have been used but water base ointments are preferred. One of the preferred compositions for a water base is glycerol monostearate. In addition polyethylene polyglycols can be used either alone or in combination with the glycerol monostearate. The average molecular weight of the polyethylene polyglycol determines the consistency and solubility of the ointment. Although a wide variety of other ointment bases may be used these embodiments are sufficiently exemplary to provide a working knowledge of the type of ointment base required to one skilled in the art. Usually 20% of the glycerol monostearate is used and the remainder is made up with water.

The following examples are embodiments of the invention which have been utilized and serve merely to indicate the variety of ointment formulas which express the spirit and principle of the invention. The examples are not meant to limit in any way the spirit or scope of the invention as expressed in the specification and appended claims. These examples are given merely to serve as a guide to one skilled in the art and to increase an understanding of the principles of the invention.

Example 1 Percent Aluminum salt of alpha-hydroxypropionic acid 2 Ethylamino benzoate 3 Dioctyl sodium sulphosuccinate /2 of 1 Glycerol monostearate 20 Water, q.s 100 Example 2 Aluminum salt of alpha-hydroxypropionic acid 8 Ethylamino benzoate 3 Dioctyl sodium sulphosuccinate /2 of 1 Glycerol monostearate 18 Water, q.s 100 This ointment is manipulated, preferably in a colloid mill, and filled into tubes for dispensing. The ointment is useful for the control of the symptoms of hemorrhoids.

Example 3 Percent Aluminum salt of alpha-hydroxypropionic acid 1 Ethylamino benzoate 3 Dioctyl sodium sulphosuccinate /2 of 1 Glycerol monostearate 18 Water, q.S 100 Example 4 Aluminum salt of alpha-hydroxypropionic acid 2 Ethylamino benzoate 5 Dioctyl sodium sulphosuccinate /2 of l Glycerol monostearate 20 Water, q.s 100 Example 5 Aluminum salt of alpha-hydroxypropionic acid 2 Eethylamino benzbate 1 /2 Dioctyl sodium sulphosuccinate /2 of 1 Glycerol monostearate 20 Water, q.s 100 Example 6 Aluminum salt of alpha-hydroxypropionic acid 2 Ethylamino benzoate 3 Dioctyl sodium sulphosuccinate 1 Glycerol monostearate 18 Water, q.s

Example 7 Aluminum salt of alpha-hydroxypropionic acid 2 Ethylamino benzoate 3 Dioctyl sodium sulphosuccinate /2 of l Glycerol monostearate 20 Water, q.s 100 Example 8 Aluminum salt of alpha-hydroxypropionic acid 2 Ethylamino benzoate 3 Sodium lauryl sulphate /2 of 1 Polyethylene polyglycol, q.s. to make a soluble soft suppository base.

Suppositories are molded by heat or stamped by machine to the desired shape. Inserted in the usual manner they provide relief from the symptoms of internal hemorrhoids.

Example 9 Percent Aluminum salt of alpha-hydroxypropionic acid 2 Z-diethyl aminoethyl ester of para aminobenzoic acid 3 Sodium carboxymethylcellulose /2 of l Glycerol monostearate 20 Water, q.s 100 Example 10 Aluminum salt of alpha-hydroxypropionic acid 2 2-butoxy-n-(2 diethyl aminoethyl) choninamide hydrochloride 3 Sodium lauryl sulphate /2 of 1 Glycerol monostearate 18 Water, q.S 100 Example 11 Aluminum salt of alpha-hydroxypropionic acid 2 2-(isobutylamino)-ethyl para aminobenzoate hydrochloride 3 Sorbitan mono-oleate polyester /2 of l Glycerol monostearate 20 Water, q.s 100 Example 12 Aluminum salt of alpha-hydroxypropionic acid 2 2-dimethyl amino ester of para butylarnino benzoic acid 3 Sodium carboxymethylcellulose /2 of 1 Glycerol monostearate 20 Water, q.s 100 Having described the invention in the above specification and having given examples of some embodiment of the invention I claim:

1. A composition adapted for the local treatment of hemorrhoids and the like, said composition consisting essentially as co-active ingredients of the aluminum salt of alpha-hydroxy-propionic acid, of a topical anesthetic selected from the group consisting of ethylamino benzoate, 2-diethyl aminoethyl ester of para-amino-benzoic acid, 2- butoxy-n-(2-diethyl aminoethyl) choninamide hydrochloride, 2-(isobutylamino)-ethyl para-amino-benzoate hydrochloride, and Z-dimethyl amino ether of para butylamino benzoic acid, and of a substance selected from the group consisting of sodium carboxymethylcellulose, methyl cellulose, dioctyl sodium sulphosuccinate, sodium lauryl sulphate, sorbitan mono-oleate and sorbitan mono-oleate polyester.

2. A composition adapted for the local treatment of hemorrhoids and the like, said composition consisting essentially as co-active ingredients of the aluminum salt of alpha-hydroXy-propionic acid, of a topical anesthetic selected from the group consisting of ethylamino benzoate, Z-diethyl aminoethyl ester of para-aminobenzoic acid, 2-butoxyn-(2-diethyl aminoethyl) choninamide hydrochloride, 2-(isobutylamino)-ethyl para-amino-benzoate hydrochloride, and Z-dimethyl amino ether of para butylamino benzoic acid and of a substance selected from the group consisting of sodium carboxymethylcellulose, methyl cellulose, dioctyl sodium sulphosuccinate, sodium lauryl sulphate, sorbitan mono-oleate and sorbitan mono-oleate polyester, said co-active ingredients being distributed in a water soluble ointment base.

3. A composition adapted for the local treatment of hemorrhoids and the like, said composition consisting essentially as co-active ingredients of the aluminum salt of alpha-hydroxy-propionic acid, ethylamino benzoate and dioctyl sodium sulphosuccinate.

4. A composition adapted for the local treatment of hemorrhoids and the like, said composition consisting essentially as co-active ingredients of l8% by Weight of the aluminum salt of alpha-hydroxypropionic acid, of 1- 5% by weight of a topical anesthetic selected from the group consisting of ethylamino benzoate, 2-diethyl aminoethyl ester of para-amino-benzoic acid, 2-butoxy-n-(2-diethyl aminoethyl) choninamide hydrochloride, 2-(isobutylamino)-ethyl para-aminobenzoate hydrochloride, and Z-dimethyl amino ether of para butylamino benzoic acid, and of 0.25-1% by weight of a substance being selected from the group consisting of sodium carboxymethylcellulose, methylcellulose, dioctyl sodium sulphosuccinate, sodium lauryl sulphate, sorbitan mono-oleate and sorbitan mono-oleate polyester; and pharmaceutical excipients.

5. A composition adapted for the local treatment of hemorrhoids and the like, said composition consisting essentially as co-active ingredients of 18% by weight of the aluminum salt of alpha-hydroxypropionic acid, 15% by weight of ethylamino benzoate and 0.25l% by weight of dioctyl sodium sulphosuccinate, and pharmaceutical excipients.

References Cited in the file of this patent UNITED STATES PATENTS 439,581 Hall Oct. 28, 1890 2,241,331 Shelton May 6, 1941 2,327,815 Niedercorn Aug. 24, 1943 OTHER REFERENCES Alprocols, Facts and Comparisons, Facts and Comparisons Inc., St. Louis, Mo., August 1955, p. 303.

Wilson: J.A.M.A., 158:4, May 28, 1955,, pp. 261-263.

Technic of Medication, 1938, p. 140.

Vallance: Manufacturing Chemist, 16:5, May 1945, pp. 157-161.

PDR, Physicians Desk Reference, Medical Economics Inc., Oradell, N. 1., copyright 1956, pp. 349, 491, 498, 582. 1 

1. A COMPOSITION ADAPTED FOR THE LOCAL TREATMENT OF HEMORRHOIDS AND THE LIKE, SAID COMPOSITION CONSISTING ESSENTIALLY AS CO-ACTIVE INGREDIENTS OF THE ALUMINUM SALT OF ALPHA-HYDROXY-PROPIONIC ACID, OF A TOPICAL ANESTHETIC SELECTED FROM THE GROUP CONSISTING OF ETHYLAMINO BENZOATE, 2-DIETHYL AMINOETHYL ESTER OF PARA-AMINO-BENZOIC ACID, 2BUTOXY-N-(2-DIETHYL AMINOETHYL) CHONINAMIDE HYDROCHLORIDE, 2-(ISOBUTYLAMINO)-ETHYL PARA-AMINO-BENZOATE HYDROCHLORIDE, AND 2-DEMETHYL AMINO ETHER OF PARA BUTYLAMINO BENZOIC ACID, AND OF A SUBSTANCE SELECTED FROM THE GROUP CONSISTING OF SODIUM CARBOXYMETHYLCELLULOSE, METHYL CELLULOSE, DIOCTYL SODIUM SULPHOSUCCINATE, SODIUM LAURYL SULPHATE, SORBITAN MONO-OLEATE AND SORBITAN MONO-OLEATE POLYESTER. 